Field of the Invention
The present invention relates to improved drug formulation methods, products formed by these methods, as well as methods of their use.
Background
Some formulated drug products are subject to chemical instability resulting in limited shelf life and potentially inaccurate drug dosing. In addition, sub-optimal rates of drug delivery to intended target tissues can result from uncontrolled drug release from the drug product. Overcoming these problems would enhance the safety and efficacy of many existing drug formulation products and new products in development.
In fact, multiple drug products have been recalled or withdrawn from the market due to low product stability. For example, products containing Liothyronine sodium, the L-isomer of triiodothyronine (T3), have had multiple recalls based on instability that resulted in lower than claimed dosing and possible formation of degradation products with unintended side effects. The brand name Cytomel® product (King/Pfizer) of Liothyronine sodium, as well as the generic version of Liothyronine sodium (Mylan, Watson and Paddock Laboratories) as referenced in the Abbreviated New Drug Applications (ANDAs) for these generic products, have all had documented problems with product stability and have been either recalled or withdrawn from the market. To claim substantial equivalence of the generic to the innovator product in the case of Cytomel®, the ANDA generic products were all required to be formulated with the same excipients (i.e., calcium sulfate, gelatin, starch, stearic acid, sucrose and talc) for bioequivalence and FDA approval. Therefore, it is not surprising that the equivalent generic product with the same Liothyronine formulation had similar instabilities as the reference drug. Likewise, multiple products other than Liothyronine sodium have also been recalled due to loss of potency.
Accordingly, there is a need in the art for improved drug formulation methods, and products formed thereby as well as uses thereof, that produce a homogeneous distribution of drug substances in a final drug product. There is also a need in the art for improved drug formulation methods that produce final drug products having a more consistent and controlled rate of drug release and/or enhanced product stability.